Narrow-band ultraviolet B treatment boosts serum 25-hydroxyvitamin D in patients with psoriasis on oral vitamin D supplementation

Ac a De m Vene eol 94 INVESTIGATIVE REPORT Ac a De m Vene eol 2014; 94: 146–151 © 2014 The Au ho s. doi: 10.2340/00015555-1685 Jou nal Compila ion © 2014 Ac a De ma o-Vene eologica. ISSN 0001-5555 A cou se o ea men wi h na ow-band ul a iole B (NB-UVB) imp o es pso iasis and inc eases se um 25-hyd oxy i amin D (25(OH)D). In his s udy 12 pa- ien s wi h pso iasis who we e supplemen ed wi h o al cholecalci e ol, 20 µg daily, we e gi en a cou se o NB- UVB and hei esponse measu ed. A baseline, se um 25(OH)D was 74.14 ± 22.9 nmol/l. A he 9 h exposu e o NB-UVB 25(OH)D had inc eased by 13.2 nmol/l (95% con idence in e al (95% CI) 7.2–18.4) and a he 18 h exposu e by 49.4 nmol/l (95% CI 35.9–64.6) abo e base- line. Pso iasis A ea Se e i y Index sco e imp o ed om 8.7 ± 3.5 o 4.5 ± 2.0 (p < 0.001). A baseline, pso iasis le- sions showed low i amin D me abolizing enzyme (CY- P27A1, CYP27B1) and high human β-de ensin-2 mRNA exp ession le els compa ed wi h hose o he heal hy subjec s. In conclusion, NB-UVB ea men signi ican ly inc eases se um 25(OH)D in pa ien s wi h pso iasis who a e aking o al i amin D supplemen a ion, and he con- cen a ions emain a om he oxici y le el. Healing pso iasis lesions show simila mRNA exp ession o i a- min D me abolizing enzymes, bu highe an imic obial pep ide le els han NB-UVB- ea ed skin in heal hy sub- jec s. Key wo ds: pso iasis; ul a iole B adia ion; i amin D; CYP27A1; CYP27B1; ca helicidin; human β-de ensin. Accep ed Ap 29, 2013; Epub ahead o p in Aug 27, 2013 Ac a De m Vene eol 2014; 94: 146–151. Timo Reunala, Depa men o De ma ology, Tampe e Uni e si y Hospi al, PO Box 2000, FIN-33521, Tampe e, Finland. E-mail: [email p o ec ed] Vi amin D insu iciency is common in Eu ope and No h Ame ica, especially du ing he win e when i amin D syn hesis induced by sunligh is ze o (1, 2). The desi able concen a ion o se um 25-hyd oxy i amin D (25(OH) D), which is he bes indica o o i amin D s a us, is s ill unde deba e. A concen a ion below 75 nmol/l (30 ng/ml) is conside ed o be insu icien o bone ac u e p e en ion (3). In addi ion o os eopo osis, low se um 25(OH)D concen a ion has ecen ly been associa ed wi h isk o colo ec al cance and ca dio ascula disease (4, 5). Vi amin D is also known o a ec skin in lamma ion and inna e o adap i e immune esponses (6, 7). Recen s udies sugges ha i amin D insu iciency is also common in pa ien s wi h pso iasis (8–10). Gisondi e al. (8) ound ha , in I aly in win e , se um 25(OH)D was below 50 nmol/l in 81% o pa ien s wi h pso iasis compa ed wi h 30% o heal hy con ols. They also sho- wed ha i amin D insu iciency was associa ed wi h pso iasis independen ly o age, sex and body mass index (BMI). Romaní e al. (10) concluded ha he insu i- ciency was also common in pa ien s wi h pso iasis and con ols in Spain, bu in hei s udy ca e ully ma ched con ols had a highe insu iciency a e han pa ien s wi h pso iasis. Na ow-band UVB (NB-UVB) pho o he apy, a wi- dely used e ec i e ea men o pso iasis (11), supp es- ses in e e on-gamma (IFN-γ) and in e leukin (IL)-17 signalling pa hways o esol e pso ia ic in lamma ion (12). NB-UVB ligh emi ing a 311–313 nm is also capable o ac i a ing i amin D syn hesis in cul u ed ke a inocy es (13). Mo eo e , se e al s udies ha e shown ha , in addi ion o healing o pso iasis, NB- UVB ea men signi ican ly inc eases se um 25(OH)D (14–17), and his inc ease co ela es wi h he ac i a ion o ci cula ing egula o y T cells (18). In e es ingly, he exp ession o ca helicidin, which is one o he mos impo an an imic obial pep ides in human skin, is dependen on 1,25-dihyd oxy i amin D (1,25(OH) 2 D) and is igge ed by UVB-induced i- amin D me abolism (6, 19). Ca helidicin and ano he inducible cu aneous an imic obial pep ide, human β-de ensin-2 (HBD2), can ac as immune- egula ing e ec o s o “ala mins” and link adap i e and inna e immune esponses (20). In addi ion, hese an imic o- bial pep ides seem o ha e a ole in he con ol o skin in lamma ion in pso iasis (21, 22). The p esen s udy examined whe he NB-UVB ea - men can inc ease se um 25(OH)D in pa ien s wi h pso- iasis who a e al eady supplemen ed wi h o al i amin D. In addi ion, we in es iga ed he e ec s o NB-UVB exposu e on cu aneous mRNA exp ession o i amin D-me abolizing enzymes and an imic obial pep ides. Na ow-band Ul a iole B T ea men Boos s Se um 25-hyd oxy i amin D in Pa ien s wi h Pso iasis on O al Vi amin D Supplemen a ion Me i J. ALA-HOUHALA1,2, Toni T. KARPPINEN3, Ka ja VäHäVIHU4, Hannu KAUTIAINEN5, Y onne DOMBROwSKI6, E na SNELLMAN3, Jü gen SCHAUBER6 and Timo REUNALA1,2 1Depa men o De ma ology, Tampe e Uni e si y Hospi al, 2Medical School, Uni e si y o Tampe e, Tampe e, Depa men s o De ma ology, 3Päijä -Häme Cen al Hospi al, Lah i,4Kan a-Häme Cen al Hospi al, Hämeenlinna, 5Uni s o P ima y Heal h Ca e, Helsinki and Tu ku Uni e si y Hospi als, and Depa - men o Gene al P ac ice, Uni e si y o Helsinki, Finland, and 6Depa men o De ma ology and Alle gy, Ludwig-Maximilian-Uni e si y, Munich, Ge many 147 Na ow-band UVB and i amin D in pso iasis METHODS Pa ien s wi h pso iasis and heal hy subjec s A o al o 12 pa ien s wi h pso iasis (mean age 42.8 yea s; Table I) pa icipa ed in he s udy. Fou pa ien s had also pso ia ic a h i is, bu none o hem ecei ed any sys emic d ug ea men because hei a h i is was no ac i e du ing he s udy. Inclu- sion c i e ia we e no pho o he apy, sola ium o sunny holidays du ing he 2 p eceding mon hs. Be o e he NB-UVB cou se he pa ien s had used cholecalci e ol 20 µg (800 IU) daily o a mean o 3.3 mon hs (Table I). Fi een nu ses and o he hospi al employees (mean age 46.1 yea s; Table I) olun ee ed as con- ols in he s udy. These subjec s had used o al cholecalci e ol o a mean o 3.4 mon hs (Table I). The pa ien s wi h pso iasis and he heal hy subjec s con inued o use o al cholecalci e ol du ing he NB-UVB cou se and subsequen o i . The s udy p o ocol was app o ed by he e hics commi ee o Tampe e Uni e si y Hospi al and all subjec s ga e hei in o med consen o pa icipa e. The s udy p o ocol ollowed he p inciples o he Decla a ion o Helsinki. Na ow-band UVB exposu e The s udy was pe o med in win e om Decembe 2011 o Ap il 2012 in o de o exclude he e ec o he sun. The s udy subjec s ecei ed NB-UVB exposu e 3 imes a week on he whole body a ea wi h a Waldmann UV 7001 cabin equipped wi h 40 TL01 ubes (Schulze & Böhm, B ühl, Ge many). The i s NB-UVB dose was 0.19 J/cm2 (1.11 s anda d e y hema dose (SED)) and i was g adually inc eased each ime, acco ding o a ixed p o ocol, up o 9 exposu es, i.e. o 0.97 J/cm2 (5.70 SED). I he subjec s expe ienced mild i ching o e y hema, he nex NB-UVB dose was ei he no inc eased o was educed. This was he case in 6 pa ien s wi h pso iasis and 8 heal hy subjec s. The ea e , he NB-UVB ea men was gi en only o pa ien s wi h pso iasis un il he ash was almos o o ally clea ed. This ook a mean o 20.5 ( ange 11–31) NB-UVB exposu es. Clinical imp o emen was measu ed wi h he Pso iasis A ea Se e i y Index (PASI) sco e. The mean cumula i e dose o NB-UVB gi en o he 12 pa ien s wi h pso iasis du ing 9 exposu es was 4.49 ± 0.44 J/cm2 and o he 9 pa ien s du ing 18 exposu es 15.63 ± 1.67 J/cm2. These doses a e equi alen o 26.4 ± 2.6 SED and o 91.9 ± 9.8 SED, espec i ely. One SED is equi alen o 10 mJ/cm2 Commission In e na ionale de l’Eclai age (CIE) e y hema-weigh ed i adiance. In he 15 heal hy subjec s he mean cumula i e dose o 9 NB-UVB exposu es was 4.37 ± 0.55 J/cm2, which is equi alen o 25.7 ± 3.2 SED. The cu- mula i e NB-UVB doses gi en up o 9 exposu es o he pa ien s wi h pso iasis and heal hy subjec s did no di e (p = 0.57). Measu emen o se um 25-hyd oxy i amin D concen a ions Blood samples o se um 25(OH)D measu emen s we e aken a baseline, and a 9 h and 18 h NB-UVB exposu es. Follow-up samples we e aken one mon h a e he NB-UVB cou se. The samples we e p o ec ed om ligh , cen i uged and hen s o ed a –70ºC. Se um 25(OH)D concen a ion was analysed in du- plica es using adioimmunoassay (Immunodiagnos ic Sys ems, Boldon, UK), as desc ibed p e iously (23). Skin biopsies and quan i a i e eal- ime PCR Punch biopsies we e aken om skin lesions o 12 pa ien s wi h pso iasis (8 om he bu ocks, 2 om elbows, and 2 om lowe back) and om he bu ocks o 13 heal hy subjec s a baseline and a he 9 h NB-UVB exposu e. The biopsies we e immedia ely ozen and s o ed a –70ºC. To al RNA om biopsies was iso- la ed using TRIsu e Reagen (Bioline, Luckenwalde, Ge many) and 1 µg o RNA was e e se- ansc ibed wi h High Capaci y cDNA Re e se T ansc ip ion Ki (Applied Biosys ems, Fos e Ci y, CA, USA) o cDNA. The mRNA exp ession le els o CYP27A1 and CYP27B1 enzymes, and an imic obial pep ides ca helicidin and HBD2 we e e alua ed using a Ligh Cycle ® 2.0 sys em and he co esponding human Uni e sal P obe Lib a y Se (Roche), as desc ibed p e iously (15). S a is ical analysis S a is ical compa ison be ween he g oups was pe o med by S uden ’s - es , pe mu a ion es o χ2 es , when app op ia e. The changes wi hin pa ien s wi h pso iasis and heal hy sub- jec s we e analysed by applying a pe mu a ion es o ela ed samples. Repea ed measu es we e analysed using gene alizing es ima ing equa ion models wi h he uns uc u ed co ela ion s uc u e using boo s ap- ype s anda d e o . RESULTS Se um 25(OH)D concen a ions a baseline, du ing and a e NB-UVB cou se A baseline, se um 25(OH)D concen a ion was 74.14 ± 22.9 nmol/l (mean ± SD) in he 12 pa ien s wi h pso iasis and 74.30 ± 14.8 nmol/ in he 15 heal hy subjec s. A 9 h NB-UVB exposu e se um 25(OH)D had inc eased by 13.2 nmol/l (95% CI 7.2–24.9, p = 0.0029) in he pa ien s wi h pso iasis and by 17.0 nmol/l (95% CI 6.7–21.0, p < 0.001) in he heal hy subjec s (Fig. 1, Table II). A 18 h NB-UVB exposu e 25(OH)D had inc eased by 49.4 nmol/l (95% CI 35.9–64.6, p = 0.0039) in he 9 pa ien s wi h pso iasis (Table II). PASI sco e imp o ed in he pa ien s wi h pso iasis om 8.7 ( ange 4.0–16.2) a baseline o 6.4 ( ange 2.1–12.8) a 9 h and o 4.5 ( ange 1.1–8.2) a 18 h exposu e (p < 0.001; Table II). One mon h a e NB-UVB exposu e, se um 25(OH)D was s ill inc eased om baseline by 29.9 nmol/l (95% CI 13.6–49.0; p = 0.0078) in he 8 pa ien s wi h pso iasis and by 17.5 nmol/l (95% CI 10.1–24.9; p < 0.001) in he 15 heal hy subjec s (Table II). An imic obial pep ide and enzyme mRNA exp ession in skin biopsy specimens A baseline, he mRNA exp ession le els o CYP27A1 and CYP27B1 we e signi ican ly lowe (p < 0.001) in Table I. Demog aphy and use o o al cholecalci e ol be o e na ow- band ul a iole B (NB-UVB) cou se in 12 pa ien s wi h pso iasis and 15 heal hy subjec s Pso iasis pa ien s Heal hy subjec s p- alue Male/ emale, n7/5 1/14 0.008 Age, yea s, mean ± SD 42.8 ± 14 46.1 ± 11 0.47 Body mass index, kg/m2, mean ± SD 29.6 ± 5.4 23.4 ± 3.8 0.002 Fi zpa ick skin ype II/III/IV, n3/6/3 3/10/2 0.66 O al cholecalci e ol, 20 µg daily be o e NB-UVB cou se, mon hs, mean ( ange) 3.3 (1–24) 3.4 (1–24) 0.75 SD: s anda d de ia ion. Ac a De m Vene eol 94 148 M. J. Ala-Houhala e al. he pa ien s wi h pso iasis han in heal hy subjec s (Fig. 2A and B, Table III). A baseline ca helicidin mRNA exp ession le els we e simila in he pso iasis lesions and in he no mal skin o heal hy subjec s, whe eas HBD2 mRNA le els we e signi ican ly (p < 0.001) highe in he pso iasis lesions (Fig. 2C, Table III). NB-UVB exposu e did no change CYP27A1, CYP27B1 and ca helidicin mRNA exp ession le els in he pa ien s wi h pso iasis, bu a signi ican (p = 0.002) dec ease was seen in he HBD2 mRNA exp ession le el (Fig. 2 and Table III). In he heal hy subjec s NB-UVB exposu e signi ican ly dec eased CYP27A1, CYP27B1 and ca helidicin mRNA exp ession le els, while HBD2 inc eased sligh ly (Fig. 2, Table III). DISCUSSION Se e al ecen s udies ha e demons a ed ha NB-UVB, a widely used ea men o pso iasis (11), signi ican ly imp o es se um 25(OH)D concen a ions, especially du ing he win e (10, 14–17). The numbe o NB-UVB exposu es gi en in hese pso iasis s udies a ied om 15 o 27 and he inc ease in se um 25(OH)D anged om 66% o 163% (Table IV). In con as o hese p e ious s udies, he p esen pa ien s wi h pso iasis we e addi io- nally supplemen ed wi h o al 20 µg o cholecalci e ol daily o a mean o 3.3 mon hs be o e en y in o he ial. Due o his p e- ea men hei mean se um 25(OH)D was 74 nmol/l a baseline, which is wice as high as in ou p e ious s udy (14). Ne e heless, UVB ea men u he inc eased se um 25(OH)D, by 17% a he 9 h and by 58% a he 18 h NB-UVB exposu e. Al hough he BMI was signi ican ly lowe in he heal hy subjec s han in he pa ien s wi h pso iasis, he baseline 25(OH)D concen a ion and he inc ease a 9 h NB-UVB exposu e was o app oxima ely he same magni ude. This inding is somewha unexpec ed because obese subjec s a e mo e p one o i amin D insu iciency due o he deposi ion o i amin D p ecu so s in a issue (2, 24). In a ecen s udy (25) in which subjec s we e supplemen ed wi h 15 µg o al cholecalci e ol daily, BMI in olde , bu no in younge , adul s was shown o be nega i ely associa ed wi h he change in se um 25(OH)D. These esul s indica e ha BMI is impo an when pe o ming i amin D s udies, and i amin D insu iciency epo ed in some pso iasis s udies could be a ibu ed o obesi y and como bidi ies associa ed wi h se e e pso iasis. The limi a ion o he p esen s udy is ha he pa ien s wi h pso iasis and he heal hy subjec s we e no ma ched o BMI. Howe e , he simila and signi ican inc eases in se um 25(OH) D le els in bo h g oups who we e con inuously supple- men ed wi h a a he high dose o o al i amin D indica e ha NB-UVB exposu e is an e icien way o imp o e i amin D balance. In ag eemen wi h his, 2 ecen s udies in heal hy subjec s ha e documen ed he supe i- o i y o NB-UVB exposu e o e o al supplemen a ion o cholecalci e ol, 20 µg and 40 µg daily, o imp o e se um 25(OH)D concen a ion (23, 26). In he p esen s udy he mean inc ease in se um 25(OH)D a he 18 h NB-UVB exposu e was 58% and he highes indi idual concen a ion measu ed 155 nmol/l. O e all, he inc ease obse ed was no as ma ked as in p e ious pso iasis s udies (Table IV). This is no unexpec ed, because i appea s o be e iden ha he lowe he s a ing 25(OH)D concen a ion he highe Table II. Na ow-band UVB (NB-UVB) doses, se um 25-hyd oxy i amin D (25(OH)D) concen a ions and Pso iasis A ea Se e i y Index (PASI) sco es in 12 pa ien s wi h pso iasis and 15 heal hy subjec s A baseline A 9 h NB-UVB exposu e A 18 h NB-UVB exposu e 1 mon h a e NB-UVB cou se Pa ien s wi h pso iasis, n To al NB-UVB dose, J/cm2, mean ± SD 25(OH)D; nmol/l, mean ± SD PASI sco e, mean ± SD 12 – 74.1 ± 22.9 8.7 ± ±3.5 12 4.5 ± 0.4 87.3 ± ± 16.0 6.4 ± 3.1 9 15.6 ± 1.7 117.3 ± 28.9 4.5 ± 2.0 8 – 115.0 ± 26.5 – Heal hy subjec s, n To al NB-UVB dose, J/cm2 25(OH)D, nmol/l, mean ± SD 15 – 74.3 ± 14.8 15 4.37 ± 0.6 91.3 ± 17.1 – 15 – 88.3 ± 19.9 Fig. 1. Se um 25-hyd oxy i amin D (25(OH)D) concen a ions be o e and a 9 h (a e ) na ow-band ul a iole B (NB-UVB) exposu e in 12 pa ien s wi h pso iasis and 15 heal hy subjec s. The pa ien s wi h pso iasis and heal hy subjec s ecei ed o al cholecalci e ol, 20 µg daily. The inc ease is signi ican in he pa ien s wi h pso iasis (p = 0.003) and heal hy subjec s (p < 0.001). L Ac a De m Vene eol 94 149 Na ow-band UVB and i amin D in pso iasis he esponse o UVB ea men (27). Mo eo e , he e is e idence ha du ing UVB exposu e o he skin, bu no du ing o al supplemen a ion, a nega i e eedback mechanism con ols i amin D syn hesis o p e en o e dosing and i amin D oxici y (28). I is no ewo - hy in his con ex , ha 1 o he p esen pa ien s had an excep ionally high le el o se um 25(OH)D, i.e.130 nmol/l a baseline and she was he only one o espond o NB-UVB exposu e wi h dec eased se um 25(OH)D. In addi ion, al hough he pa ien s and heal hy subjec s con inued wi h o al cholecalci e ol supplemen a ion, se um 25(OH)D concen a ions s a ed o dec ease one mon h a e NB-UVB exposu e. This is in ag eemen wi h ou p e ious NB-UVB s udies (15, 23) and demon- s a es ha e en a he high con inuous o al i amin D supplemen a ion is no su icien o main ain se um 25(OH)D le els achie ed by a sho cou se o NB-UVB exposu e. I has been epo ed ha NB-UVB exposu e gi en wice a mon h main ains he le els o 25(OH) D achie ed in he summe (29). The e o e, a simila schedule could be applicable o he NB-UVB- ea ed pa ien s wi h pso iasis du ing he win e in o de o main ain su icien i amin D. A p e ious s udy in UVB- ea ed o gan cul u es sho- wed ha CYP27A1 and CYP27B1 in he ke a inocy es a e capable o hyd oxyla ing p ecu so s in o he ac i e o m o i amin D, i.e. 1,25(OH) 2 D (13). Thus, bo h enzymes could be ega ded as su oga e ma ke s o i amin D me abolism. In he p esen s udy he exp es- sion le els o CYP27A1 and CYP27B1 a baseline we e low in he pso ia ic lesions compa ed wi h heal hy skin and did no change du ing NB-UVB ea men . A i s , he low baseline le el o CYP27B1 in pso iasis lesions seems di icul o explain. Howe e , he pa ien s wi h pso iasis we e supplemen ed wi h o al cholecalci e ol, and i could be ha he me abolism o i amin D in he pso iasis lesions is a mo e ac i e han in he no mal skin o heal hy subjec s. Due o his, he low CYP27A1 and CYP27B1 ac i i ies in he pso iasis lesions a baseline and a e NB-UVB exposu e, and also in he no mal skin a e NB-UVB exposu e, could be due o a e y sensi i e na u al eedback con olling mechanism in cu aneous i amin D syn hesis (6, 7). An imic obial pep ides seem o ha e a ole in he pa hogenesis o skin in lamma ion in pso iasis (21, 30). In ag eemen wi h ou p e ious s udy (15), we ound in pso iasis lesions a baseline signi ican ly inc eased mRNA exp ession o HBD2. we could also show ha epea ed NB-UVB exposu e educed HBD2 exp ession in healing pso iasis lesions. In con as o HBD2, we ound no inc eased mRNA exp ession o ca helicidin in he pso iasis lesions, ei he a baseline o a e NB- UVB exposu e. This is su p ising wi h ega d o he indings o ou p e ious s udy (15). The con inuous Table III. Vi amin D me abolizing enzyme and an imic obial pep ide mRNA exp ession le els in he pso iasis lesions o 12 pa ien s and no mal skin o 13 heal hy subjec s a baseline and a 9 h na ow-band UVB (NB-UVB) exposu e Pso iasis p- alue Heal hy subjec s p- alue Baseline Mean ± SD A 9 h NB-UVB Mean ± SD Baseline Mean ± SD A 9 h NB-UVB Mean ± SD CYP27A1 0.16 ± 0.85 0.23 ± 0.13 0.17 1.05 ± 0.34 0.43 ± 0.14 < 0.001 CYP27B1 0.69 ± 0.14 0.60 ± 0.18 0.070 1.04 ± 0.35 0.63 ± 0.18 0.0017 Ca helicidin 1.81 ± 1.51 1.70 ± 1.58 0.88 1.32 ± 0.99 0.12 ± 0.08 < 0.001 Human β-de ensin-2 41,739 ± 65,700 1,497 ± 1,037 0.002 159.65 ± 302.49 471.84 ± 328.71 0.041 Fig. 2. (A) CYP27A1 mRNA, (B) CYP27B1 mRNA and (C) ca helicidin mRNA exp ession le els in skin lesions o pa ien s wi h pso iasis (n = 12) and no mal skin o heal hy subjec s (n = 13) be o e and a 9 h (a e ) na ow-band ul a iole B (NB-UVB) exposu e. Be o e NB-UVB cou se he CYP27A1 and CYP27B1 le els a e signi ican ly lowe (p < 0.001), bu he ca helidicin le els do no di e (p = 0.34) in he pa ien s wi h pso iasis compa ed wi h he heal hy subjec s. NB-UVB exposu e did no change CYP27A1 mRNA, CYP27B1 mRNA o ca helidicin mRNA le els in he pa ien s wi h pso iasis (A: p = 0.17; B: p = 0.070; C: p = 0.88) bu he dec ease is signi ican (A: p < 0.001; B: p = 0.002; C: p < 0.001) in he heal hy subjec s. Ac a De m Vene eol 94 150 M. J. Ala-Houhala e al. o al supplemen a ion wi h i amin D be o e he s udy, wi h possible accumula ion o i amin D p ecu so s and 1,25(OH) 2 D in he pso iasis lesions and ac i a ion o nega i e eedback mechanisms, could again be a eason o his inding. O e all, he p esen ca helidicin and i amin D-me abolizing enzyme gene exp ession esul s sugges ha he no mal skin o heal hy subjec s eac s mo e ac i ely o NB-UVB exposu e han he in lamed skin o pso iasis lesions. I is, howe e , no ewo hy ha in spi e o hese gene exp ession di e ences he pa ien s wi h pso iasis and heal hy subjec s showed simila NB- UVB esponses in he se um 25(OH)D concen a ion. Knowledge o he isk o i amin D insu iciency is well-accep ed. In Finland, o example, he e a e ecom- menda ions o child en and p egnan women o use up o 10 µg and o elde ly people up o 20 µg daily o o al i amin D supplemen a ion (31). Mo eo e , i amin D p oduc s a e ac i ely ma ke ed and olun a y supple- men a ion especially du ing win e mon hs is now also common among de ma ological pa ien s. Many pa ien s wi h pso iasis will ecei e NB-UVB ea men , which is e ec i e and, in he sho - e m, is conside ed sa e wi h ega d o isk o skin malignancy (32, 33). The p esen NB-UVB s udy documen ed ha e en hough he pa- ien s wi h pso iasis ecei ed o al cholecalci e ol 20 µg daily hei se um 25(OH)D concen a ions emained a om 250 nmol/l. Le els below his a e conside ed sa e wi h ega d o oxici y (34) and, he e o e, we conclude ha he e is no need o s op olun a y o al i amin D supplemen a ion whene e pa ien s wi h pso iasis need o s a NB-UVB ea men . In addi ion, in he p esen s udy pa ien s wi h pso iasis supplemen ed wi h o al cholecalci e ol showed a simila signi ican dec ease in PASI sco e, as did he pa ien s wi h no o al i amin D supplemen a ion in ou p e ious s udy (15). This sugges s ha he esponse o NB-UVB ea men in pso iasis is no dependen on whe he he pa ien is supplemen ed wi h o al i amin D. In conclusion, his s udy showed ha , al hough he pa ien s wi h pso iasis ecei ed con inuous o al cholecalci e ol supplemen a ion, NB-UVB exposu e inc eased se um 25(OH)D concen a ion by 58%. In healing pso iasis lesions NB-UVB ea men did no al e he exp ession o i amin D-me abolizing enzyme and ca helidicin mRNA, bu dec eased he exp ession o HBD2 mRNA. ACKNOWLEDGEMENTS This s udy was suppo ed by Na ional G adua e School o Clinical In es iga ion (M.A-H), and by Compe i i e Resea ch Funding o he Tampe e Uni e si y Hospi al (G an s 9K104 and 9M089). The au ho s would like o hank nu ses Pi jo Honko and Tuija Valjakka o p o iding he NB-UVB exposu e in he s udy. The au ho s decla e no con lic s o in e es . REFERENCES 1. Holick MF, Chen TC. Vi amin D de iciency: a wo ldwide p oblem wi h heal h consequences. Am J Clin Nu 2008; 87: 1080S–1086S. 2. Hyppönen E, Powe C. Hypo i aminosis D in B i ish adul s a age 45 y: na ionwide coho s udy o die a y and li es yle p edic o s. Am J Clin Nu 2007; 85: 860–868. 3. Bischo -Fe a i HA, Gio annucci E, wille wC, Die ich T, Dawson-Hughes B. Es ima ion o op imal se um con- cen a ions o 25-hyd oxy i amin D o mul iple heal h ou comes. Am J Clin Nu 2006; 84: 18–28. 4. Gandini S, Boniol M, Haukka J, By nes G, Cox B, Sneyd MJ, e al. Me a-analysis o obse a ional s udies o se um 25-hyd oxy i amin D le els and colo ec al, b eas and p os a e cance and colo ec al adenoma. In J Cance 2011; 128: 1414–1424. 5. Pi as AG, Chung M, T ikalinos T, Mi i J, B endel M, Pa el K, e al. Sys ema ic e iew: Vi amin D and ca diome abolic ou comes. Ann In e n Med 2010; 152: 307–314. 6. Schaube J, Do schne RA, Coda AB, Büchau AS, Liu PT, Kiken D, e al. Inju y enhances TLR2 unc ion and an imi- c obial pep ide exp ession h ough a i amin D-dependen mechanism. J Clin In es 2007; 117: 803–811. 7. Lehmann B, Meu e M. Vi amin D me abolism. De ma ol The 2010; 23: 2–12. 8. Gisondi P, Rossini M, Di Cesa e A, Idolazzi L, Fa ina S, Bel ami G, e al. Vi amin D s a us in pa ien s wi h ch onic plaque pso iasis. B J De ma ol 2012; 166: 505–510. 9. O gaz-Molina J, Buendía-Eisman A, A abal-Polo MA, Ruiz JC, A ias-San iago S, e al. De iciency o se um con- cen a ion o 25-hyd oxy i amin D in pso ia ic pa ien s: a case-con ol s udy. J Am Acad De ma ol 2012; 67: 931–938. Table IV. Na ow-band UVB (NB-UVB) ea men s gi en in di e en s udies o pa ien s wi h pso iasis in win e signi ican ly inc ease se um 25-hyd oxy i amin D (25(OH)D) concen a ion Pa ien s n NB-UVB ea men s n 25(OH)D a baseline nmol/l Mean ± SD 25(OH)D a he end nmol/l Mean ± SD Inc ease % P esen s udy, Finlanda12 9 9 18 74.1 ± 22.9 87.3 ± 16.0 117.3 ± 28.9 17 58 Romani e al., 2012 (10), Spain 50 27b36.0 ± 26.3 77.0 ± 33.5 113 Lesiak e al., 2011 (17), Poland 17 17 10 20 60.5 101.8 106.8 68 73 Ryan e al., 2010 (16), I eland 29 18b57.5 147.5 155 Vähä ihu e al., 2010 (15), Finland 18 15 36.8 ± 12.5 96.7 ± 13.4 163 Osmance ic e al., 2009 (14), Sweden 18 26b71 ± 17 118 ± 39 66 aPa ien s supplemen ed wi h o al cholecalci e ol, 20 µg daily. bMean. Ac a De m Vene eol 94 151 Na ow-band UVB and i amin D in pso iasis 10. Romaní J, Caixàs A, Ca ascosa JM, Ribe a M, Rigla M, Luelmo J. E ec o na owband ul a iole B he apy on in lamma o y ma ke s and body a composi ion in mode a e o se e e pso iasis. B J De ma ol 2012; 166: 1237–1244. 11. Bandow GD, Koo JY. Na ow-band ul a iole B adia ion: a e iew o he cu en li e a u e. In J De ma ol 2004; 43: 555–561. 12. Rácz E, P ens EP, Ku ek D, Kan M, de Ridde D, Mou i s S, e al. E ec i e ea men o pso iasis wi h na ow-band UVB pho o he apy is linked o supp ession o he IFN and Th17 pa hways. J In es De ma ol 2011; 131: 1547–1558. 13. Lehmann B, Knuschke P, Meu e M. The UVB-induced syn hesis o i amin D3 and 1α,25-dihyd oxy i amin D3 (calci iol) in o gano ypic cul u es o ke a inocy es: E ec- i eness o he na owband Philips TL-01 lamp (311nm). S e oid Biochem Molec Biol 2007; 103: 682–685. 14. Osmance ic A, Landin-Wilhelmsen K, La kö O, Wennbe g AM, K ogs ad AL. Vi amin D p oduc ion in pso iasis pa- ien s inc eases less wi h na owband han wi h b oadband ul a iole B pho o he apy. Pho ode ma ol Pho oimmunol Pho omed 2009; 25: 119–123. 15. Vähä ihu K, Ala-Houhala M, Pe ic M, Kau iainen H, Hasan T, Snellman E, e al. Na owband ul a iole B ea men imp o es i amin D balance and al e s an imic obial pep ide exp ession in skin lesions o pso iasis and a opic de ma i is. B J De ma ol 2010; 163: 321–328. 16. Ryan C, Mo an B, McKenna MJ, Mu ay BF, B ady J, Col- lins P, e al. The e ec o na owband UV-B ea men o pso iasis on i amin D s a us du ing win e ime in I eland. A ch De ma ol 2010; 146: 836–842. 17. Lesiak A, Na bu J, Pawlaczyk M, Sysa-Jed zejowska A, K zyścin J. Vi amin D se um le el changes in pso ia ic pa ien s ea ed wi h na owband ul a iole B pho o he apy a e ela ed o he season o he i adia ion. Pho ode ma ol Pho oimmunol Pho omed 2011; 27: 304–310. 18. Milliken SV, Wassall H, Lewis BJ, Logie J, Ba ke RN, Macdonald H, e al. E ec s o ul a iole ligh on human se um 25-hyd oxy i amin D and sys emic immune unc ion. J Alle gy Clin Immunol 2012; 129: 1554–1561. 19. Pe ic M, Lehmann B, Vashina G, Domb owski Y, Koglin S, Meu e M, e al. UV-B– igge ed induc ion o i amin D3 me abolism di e en ially a ec s an imic obial pep ide exp ession in ke a inocy es. J Alle gy Clin Immunol 2010; 125: 746–749. 20. Schaube J, Gallo RL. An imic obial pep ides and he skin immune de ense sys em. J Alle gy Clin Immunol 2008; 122: 261–266. 21. Hollox EJ, Hu meie U, Zeeuwen PL, Palla R, Lasco z J, Rodijk-Ol huis D, e al. Pso iasis is associa ed wi h inc eased be a-de ensin genomic copy numbe . Na Gene 2008; 40: 23–25. 22. Domb owski Y, Pe ic M, Koglin S, Kamme baue C, Göss C, Anz D, e al. Cy osolic DNA igge s in lammasome ac i a ion in ke a inocy es in pso ia ic lesions. Sci T ansl Med 2011; 3: 82 a38. 23. Ala-Houhala MJ, Vähä ihu K, Hasan T, Kau iainen H, Yli- an ila L, Viljakainen HT, e al. Compa ison o na ow-band ul a iole B exposu es and o al i amin D subs i u ion on se um 25-hyd oxy i amin D concen a ion. B J De ma ol 2012; 167: 160–164. 24. Wo sman J, Ma suoka LY, Chen TC, Lu Z, Holick MF. Dec eased bioa ailabili y o i amin D in obesi y. Am J Clin Nu 2000; 72: 690–693. 25. Fo sy he LK, Li ings one MB, Ba nes MS, Ho igan G, McSo ley EM, Bonham MP, e al. E ec o adiposi y on i- amin D s a us and he 25-hyd oxycholecalci e ol esponse o supplemen a ion in heal hy young and olde I ish adul s. B J Nu 2012; 107: 126–134. 26. Bogh MK, Gulls and J, S ensson Å, Ljungg en B, Do k- han M. Na owband ul a iole B h ee imes pe week is mo e e ec i e in ea ing i amin D de iciency han 1600 IU o al i amin D(3) pe day: a andomized clinical ial. B J De ma ol 2012; 167: 625–630. 27. Bogh MK, Schmedes AV, Philipsen PA, Thieden E, wul HC. Vi amin D p oduc ion a e UVB exposu e depends on baseline i amin D and o al choles e ol bu no on skin pigmen a ion. J In es De ma ol 2010; 130: 546–553. 28. Lehmann B. Role o he i amin D3 pa hway in heal hy and diseased skin – ac s, con adic ions and hypo heses. Clin Exp De ma ol 2009; 18: 97–108. 29. Bogh MK, Schmedes AV, Philipsen PA, Thieden E, wul HC. A small sube y hemal UVB dose e e y second week is su icien o main ain summe i amin D le els: a andomi- zed con olled ial. B J De ma ol 2012; 166: 430–433. 30. Fel on S, Na id F, Schwa z A, Schwa z T, Gläse R, Rhodes LE. Ul a iole adia ion-induced up egula ion o an imi- c obial p o eins in heal h and disease. Pho ochem Pho obiol Sci 2012; 12: 29–36. 31. Na ional Ins i u e o Heal h and wel a e. [Changes in na io- nal ecommenda ion o i amin D supplemen a ion 2011]. A ailable om: h p:⁄ ⁄www. hl. i ⁄doc ⁄ i ⁄23892 [accessed 18 Ap 2013] (in Finnish). 32. Hea n RMR, Ke AC, Rahim KF, Fe guson J, Dawe RS. Incidence o skin cance s in 3867 pa ien s ea ed wi h na ow-band ul a iole B pho o he apy. B J De ma ol 2008; 159: 931–935. 33. Pa el RV, Cla k LN, Lebwohl M, Weinbe g JM. T ea men s o pso iasis and he isk o malignancy. J Am Acad De - ma ol 2009; 60: 1001–1017. 34. Soube bielle JC, Body JJ, Lappe JM, Plebani M, Shoen eld Y, wang TJ, e al. Vi amin D and musculoskele al heal h, ca dio ascula disease, au oimmuni y and cance : ecom- menda ions o clinical p ac ice. Au oimmun Re 2010; 11: 709–715. Ac a De m Vene eol 94